metabolic phenotyping
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Author(s):  
Anna Sebestyén ◽  
Titanilla Dankó ◽  
Dániel Sztankovics ◽  
Dorottya Moldvai ◽  
Regina Raffay ◽  
...  

AbstractDespite advancements in cancer management, tumor relapse and metastasis are associated with poor outcomes in many cancers. Over the past decade, oncogene-driven carcinogenesis, dysregulated cellular signaling networks, dynamic changes in the tissue microenvironment, epithelial-mesenchymal transitions, protein expression within regulatory pathways, and their part in tumor progression are described in several studies. However, the complexity of metabolic enzyme expression is considerably under evaluated. Alterations in cellular metabolism determine the individual phenotype and behavior of cells, which is a well-recognized hallmark of cancer progression, especially in the adaptation mechanisms underlying therapy resistance. In metabolic symbiosis, cells compete, communicate, and even feed each other, supervised by tumor cells. Metabolic reprogramming forms a unique fingerprint for each tumor tissue, depending on the cellular content and genetic, epigenetic, and microenvironmental alterations of the developing cancer. Based on its sensing and effector functions, the mechanistic target of rapamycin (mTOR) kinase is considered the master regulator of metabolic adaptation. Moreover, mTOR kinase hyperactivity is associated with poor prognosis in various tumor types. In situ metabolic phenotyping in recent studies highlights the importance of metabolic plasticity, mTOR hyperactivity, and their role in tumor progression. In this review, we update recent developments in metabolic phenotyping of the cancer ecosystem, metabolic symbiosis, and plasticity which could provide new research directions in tumor biology. In addition, we suggest pathomorphological and analytical studies relating to metabolic alterations, mTOR activity, and their associations which are necessary to improve understanding of tumor heterogeneity and expand the therapeutic management of cancer.


2021 ◽  
Vol 8 ◽  
Author(s):  
Joséphine Gander ◽  
Justin Carrard ◽  
Hector Gallart-Ayala ◽  
Rébecca Borreggine ◽  
Tony Teav ◽  
...  

Coronary artery disease (CAD) remains the leading cause of death worldwide. Expanding patients' metabolic phenotyping beyond clinical chemistry investigations could lead to earlier recognition of disease onset and better prevention strategies. Additionally, metabolic phenotyping, at the molecular species level, contributes to unravel the roles of metabolites in disease development. In this cross-sectional study, we investigated clinically healthy individuals (n = 116, 65% male, 70.8 ± 8.7 years) and patients with CAD (n = 54, 91% male, 67.0 ± 11.5 years) of the COmPLETE study. We applied a high-coverage quantitative liquid chromatography-mass spectrometry approach to acquire a comprehensive profile of serum acylcarnitines, free carnitine and branched-chain amino acids (BCAAs), as markers of mitochondrial health and energy homeostasis. Multivariable linear regression analyses, adjusted for confounders, were conducted to assess associations between metabolites and CAD phenotype. In total, 20 short-, medium- and long-chain acylcarnitine species, along with L-carnitine, valine and isoleucine were found to be significantly (adjusted p ≤ 0.05) and positively associated with CAD. For 17 acylcarnitine species, associations became stronger as the number of affected coronary arteries increased. This implies that circulating acylcarnitine levels reflect CAD severity and might play a role in future patients' stratification strategies. Altogether, CAD is characterized by elevated serum acylcarnitine and BCAA levels, which indicates mitochondrial imbalance between fatty acid and glucose oxidation.


2021 ◽  
Author(s):  
Julia Brunmair ◽  
Andrea Bileck ◽  
Doreen Schmidl ◽  
Gerhard Hagn ◽  
Samuel M. Meier-Menches ◽  
...  

AbstractBackground/AimsOne goal of predictive, preventive, and personalised medicine is to improve the prediction and diagnosis of diseases, as well as to monitor therapeutic efficacy and to tailor individualised treatments with as little side effects as possible. New methodological developments should preferably rely on non-invasively sampled biofluids like sweat and tears in order to provide optimal compliance. Here we have thus investigated the metabolic composition of human tears in comparison to finger sweat and evaluated whether tear analyses may provide insight into ocular and systemic disease mechanisms.MethodsIn addition to finger sweat, tear fluid was sampled from 20 healthy volunteers using commercially available Schirmer strips. Tear fluid extraction and analysis using high-resolution mass spectrometry hyphenated with liquid chromatography was performed with optimized methods each for metabolites and eicosanoids. As second approach, we performed a clinical pilot study with 8 diabetic patients and compared them to 19 healthy subjects.ResultsTear fluid was found to be a rich source for metabolic phenotyping. Remarkably, several molecules previously identified by us in sweat were found significantly enriched in tear fluid, including creatine or taurine. Furthermore, other metabolites such as kahweol and various eicosanoids were exclusively detectable in tears, demonstrating the orthogonal power for biofluid analysis in order to gain information on individual health states. The clinical pilot study revealed that many endogenous metabolites that have previously been linked to type 2 diabetes such as carnitine, tyrosine, uric acid and valine were indeed found significantly up-regulated in tears of diabetic patients. Nicotinic acid and taurine were elevated in the diabetic cohort as well and may represent new biomarkers for diabetes specifically identified in tear fluid. Additionally, systemic medications like metformin, bisoprolol, and gabapentin, were readily detectable in tears of patients. These findings highlight the potential diagnostic and prognostic power of tear fluid analyses, in addition to the promising methodological support for pharmacokinetic studies and patient compliance control.ConclusionsTear fluid analysis may support the development of clinical applications in the context of predictive, preventive, and personalised medicine as it reveals rich molecular information in a non-invasive way.


2021 ◽  
Vol 18 (3) ◽  
pp. 302-312
Author(s):  
O. Y. Kytikova ◽  
M. V. Antonyuk ◽  
T. A. Kantur ◽  
T. P. Novgorodtseva ◽  
Y. K. Denisenko

The prevalence of metabolic syndrome (MS) has a worldwide tendency to increase and depends on many components, which explains the complexity of diagnostics and approaches to the prevention and treatment of this pathology. Age, lifestyle, socioeconomic status, insulin resistance (IR), dyslipidemia, obesity and genetic predisposition are factors influencing the risk of developing and progression of MS. Features of the distribution and dysfunction of adipose tissue are important factors in the development of IR, with obesity, as well as the risk of the formation of cardiometabolic diseases and MS. ­Understanding of mechanisms is linked to advances in metabolic phenotyping. Metabolic phenotyping of obese persons is important for the development of important diseases in relation to the study of the pathophysiology of metabolic disorders, the possible concomitant disease and the search for innovative strategies for the prevention and treatment of MS. The understanding of MS mechanisms is associated with advances in metabolic phenotyping. Therefore, the relevance of further study of the pathophysiological mechanisms underlying various metabolic phenotypes of MS is one of the promising areas of modern scientific research. This review summarizes the current literature data on the prevalence of MS depending on gender, age, population, area of residence, education, level of physical activity, and many other parameters. Metabolic risks of MS development are detailed. Biological markers of MS are considered. The necessity of metabolic phenotyping of MS has been shown, which may have potential therapeutic value.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Julia Brunmair ◽  
Mathias Gotsmy ◽  
Laura Niederstaetter ◽  
Benjamin Neuditschko ◽  
Andrea Bileck ◽  
...  

AbstractMetabolic biomonitoring in humans is typically based on the sampling of blood, plasma or urine. Although established in the clinical routine, these sampling procedures are often associated with a variety of compliance issues, which are impeding time-course studies. Here, we show that the metabolic profiling of the minute amounts of sweat sampled from fingertips addresses this challenge. Sweat sampling from fingertips is non-invasive, robust and can be accomplished repeatedly by untrained personnel. The sweat matrix represents a rich source for metabolic phenotyping. We confirm the feasibility of short interval sampling of sweat from the fingertips in time-course studies involving the consumption of coffee or the ingestion of a caffeine capsule after a fasting interval, in which we successfully monitor all known caffeine metabolites as well as endogenous metabolic responses. Fluctuations in the rate of sweat production are accounted for by mathematical modelling to reveal individual rates of caffeine uptake, metabolism and clearance. To conclude, metabotyping using sweat from fingertips combined with mathematical network modelling shows promise for broad applications in precision medicine by enabling the assessment of dynamic metabolic patterns, which may overcome the limitations of purely compositional biomarkers.


Author(s):  
Jian Jin ◽  
Banrida Wahlang ◽  
Monika Thapa ◽  
Kimberly Z. Head ◽  
Josiah E. Hardesty ◽  
...  

Metabolites ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 675
Author(s):  
Justin Carrard ◽  
Hector Gallart-Ayala ◽  
Nadia Weber ◽  
Flora Colledge ◽  
Lukas Streese ◽  
...  

Cardiometabolic diseases (CMD) represent a growing socioeconomic burden and concern for healthcare systems worldwide. Improving patients’ metabolic phenotyping in clinical practice will enable clinicians to better tailor prevention and treatment strategy to individual needs. Recently, elevated levels of specific lipid species, known as ceramides, were shown to predict cardiometabolic outcomes beyond traditional biomarkers such as cholesterol. Preliminary data showed that physical activity, a potent, low-cost, and patient-empowering means to reduce CMD-related burden, influences ceramide levels. While a single bout of physical exercise increases circulating and muscular ceramide levels, regular exercise reduces ceramide content. Additionally, several ceramide species have been reported to be negatively associated with cardiorespiratory fitness, which is a potent health marker reflecting training level. Thus, regular exercise could optimize cardiometabolic health, partly by reversing altered ceramide profiles. This short review provides an overview of ceramide metabolism and its role in cardiometabolic health and diseases, before presenting the effects of exercise on ceramides in humans.


Author(s):  
Liene Bervoets ◽  
Johannes H. Ippel ◽  
Agnieszka Smolinska ◽  
Niels van Best ◽  
Paul H. M. Savelkoul ◽  
...  

2021 ◽  
Vol 224 (18) ◽  
Author(s):  
Jocelyn P. Colella ◽  
Danielle M. Blumstein ◽  
Matthew D. MacManes

ABSTRACT Metabolism is a complex phenotype shaped by natural environmental rhythms, as well as behavioral, morphological and physiological adaptations. Metabolism has been historically studied under constant environmental conditions, but new methods of continuous metabolic phenotyping now offer a window into organismal responses to dynamic environments, and enable identification of abiotic controls and the timing of physiological responses relative to environmental change. We used indirect calorimetry to characterize metabolic phenotypes of the desert-adapted cactus mouse (Peromyscus eremicus) in response to variable environmental conditions that mimic their native environment versus those recorded under constant warm and constant cool conditions, with a constant photoperiod and full access to resources. We found significant sexual dimorphism, with males being more prone to dehydration than females. Under circadian environmental variation, most metabolic shifts occurred prior to physical environmental change and the timing was disrupted under both constant treatments. The ratio of CO2 produced to O2 consumed (the respiratory quotient) reached greater than 1.0 only during the light phase under diurnally variable conditions, a pattern that strongly suggests that lipogenesis contributes to the production of energy and endogenous water. Our results are consistent with historical descriptions of circadian torpor in this species (torpid by day, active by night), but reject the hypothesis that torpor is initiated by food restriction or negative water balance.


2021 ◽  
Author(s):  
Benjamin J. Blaise ◽  
Gonçalo D. S. Correia ◽  
Gordon A. Haggart ◽  
Izabella Surowiec ◽  
Caroline Sands ◽  
...  

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